The broad objective of the proposed work is to determine optimum nanoemulsion formulations that effectively disrupt or prevent the formation and growth of oral biofilms associated with dental caries, and also to understand the mechanisms involved in their disruption. The incidence of dental caries in the population is still high. The average adult in the U.S. has from 10 to 17 decayed, missing or filled permanent teeth. Nanoemulsions are surfactant-containing oil-in-water emulsions (droplet size 400-800 nm) that are non-toxic to animals but very effective against bacteria, fungi, viruses and spores in their free-floating form. Specific Aim 1: Determine optimum nanoemulsion formulations that prevent the formation and growth of, and disrupt the presence of mixed-organism biofilms in vitro. Specific Aim 2: Investigate the effectiveness of selected nanoemulsions in a study involving rats. Specific Aim 3: Evaluate the in vitro susceptibility of biofilms to nanoemulsions when biofilms are grown under varying physiological conditions likely to be present in the oral cavity (high-low sucrose, high-low iron, high-low osmolarity, high-low oxygen), and also investigate changes in biofilm structure and community profiles. Both S. mutans in pure culture and defined mixed-organism cultures will be investigated. Specific Aim 4: Determine the mechanism of action of the nanoemulsion effect on S. mutans. The proposed work is innovative because the effects of antimicrobial nanoemulsions on biofilms common to the oral cavity have not been investigated. My goal is to be an academic biomaterials scientist with an independent research effort in the treatment and prevention of intra-oral biofilms, and the investigation of mechanisms involved in their disruption. I have successfully found expert collaborators at UTHSCSA and Texas State University for this interdisciplinary project. A K08 award will allow me to acquire the necessary microbiology and molecular biology background and laboratory techniques to successfully complete the proposed work, and will also allow me to utilize the benefits of mentoring during the transition to an independent research career. This research studies a new method of preventing tooth decay. Success may alleviate this problem, which affects a majority of people. [unreadable] [unreadable] [unreadable]